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2008 Grants - McGuire
Loss of C5L2 and NFT Formation: Conversion of Mild Cognitive Impairment to Alzheimer's Disease
Susan O. McGuire, Ph.D.
The Board of Trustees of the University of Illinois - Chicago
2008 Investigator-Initiated Research Grant
A growing body of research suggests that brain inflammation is a key hallmark of early Alzheimer's disease. Some scientists believe that the loss of nerve cells in the locus ceruleus (LC), a region of the brain that lies near the brain stem, may stimulate this process. LC nerve cell loss may lead to the reduction of C5L2, a protein shown to inhibit inflammation and protect neurons in various parts of the brain.
In preliminary research, Susan O. McGuire, Ph.D., and colleagues studied autopsied brain tissue from people with late-stage Alzheimer's disease. These tissues showed considerable losses in C5L2 levels. Furthermore, C5L2 losses appeared to be greatest in areas of the brain that developed neurofibrillary tangles. Such tangles, another hallmark of Alzheimer's, are caused by the accumulation of abnormal forms of tau protein. The researchers hypothesize that reduced C5L2 levels may lead to tangle formation as well as inflammation.
For their proposed study, Dr. McGuire and colleagues will further test this hypothesis using autopsied brain tissue from people with Alzheimer's disease or mild cognitive impairment, a condition that often precedes Alzheimer's. The researchers hope to show that C5L2 is a key biological mechanism preventing the development of early Alzheimer's.